Pernasal administration or inhalative (transpulmonary) administration of a drug by way of a patient's nose or mouth has been adapted generally as an administration method exclusively for local therapy such as therapy of rhimitis or asthma. However such a method has attracted attention in recent years as a method not only for local therapy but also as a method of administering a drug with expected systemic action that has been considered only possible by injection, such as a peptide type drug or an immediate acting drug.
As a method of pernasal administration or inhalative administration, a patient would generally inhale a drug dispensed from an application device such as an applicator or a respiratory gas mixer from a nose or mouth to the site of administration. An administration device proposed by the present applicant is adapted such that when a capsule filled with a predetermined amount of a powder drug is loaded into the device, the capsule is perforated with apertures on both ends thereof, the powder drug in the apertured capsule is driven out by a pressurized air supplied from a rubber pump, etc. and then sprayed from a nozzle inserted into a patient's nasal cavity or oral cavity (refer to Patent Documents 1 and 2).
[Patent Document 1]
JP-A No. 2005-168513
[Patent Document 2]
JP-A No. 2005-261770
By the way, a newly developed effective ingredient in a natural substance or a newly developed chemical synthesis drug require precise determination of its pharmaceutical effects and side effects through pharmacological experiments using experimental animals. Also, when investigating the effect of a chemical on the human body, precise evaluation is required using experimental animals. For this purpose, when screening a new drug with an aim of pernasal administration or inhalative administration, or in such case as investigation of the effect of a chemical in atmospheric air on the inside of a nasal cavity or a lung, it is necessary to administer the drug or the chemical into the nasal cavity or into the lung of experimental animals such that it is uniformly distributed therein. If the test substance is administered such that it is unevenly concentrated in a certain region of the nasal cavity or the lung for a local therapy, it may possibly induce significant local irritation or result in insufficient therapeutic effect. Also such uneven administration for a systemic therapy would reduce the effective surface area of the mucosal membrane that contributes to absorption, which may hinder the confirmation of toxicity that would have been observed ordinarily in human or the confirmation of the absorption ratio or therapeutic effect that would have been attained ordinarily in human.
Particularly, different from human, an experimental animal does not inhale a drug from a nose or a mouth on its own will and, when the body is constrained to carry out the experiment. If the animal is constrained for a long time, breathing may become erratic due to stress. Accordingly, it has been extremely difficult to administer a necessary amount of a test substance such that it is distributed uniformly from the nose or the mouth into the nasal cavity or into the lung thereof.
That is, to precisely evaluate and demonstrate the pharmaceutical effect, side effect, toxicity, etc. of a test substance which is dosed by pernasal administration or inhalative administration into the nasal cavity or into the lung of an experimental animal, it is necessary to administer a necessary amount of the test substances such that it is distributed uniformly into the nasal cavity or into the lung. In the pernasal administration or inhalative administration, the dosage or the distribution of the test substance administered into the nasal cavity or into the lung changes depending on the timing with respect to respiration. If the timing is incorrect, a portion of the test substance may possibly scatter to other locations and the necessary amount of the test substance would not be administered into the nasal cavity or into the lung, or the test substance may become unevenly concentrated in a certain part of the nasal cavity or in the lung. Accordingly, while the test substance has to be administered at an appropriate timing according to the respiratory state of an experimental animal, it is extremely difficult to administer the test substance at a precise timing and this results in a problem that the necessary amount of a test substance cannot be administered reliably.